(Study: Vertex IIS) Does Ivacaftor Alter Wild Type CFTR-Open Probability In The Sweat Gland Secretory Coil?
|ClinicalTrials.gov Identifier: NCT02310789|
Recruitment Status : Completed
First Posted : December 8, 2014
Results First Posted : April 20, 2018
Last Update Posted : January 9, 2019
Clinical studies of lumacaftor + ivacaftor (combo therapy) produced better FEV1 (forced expiratory volume in 1 second) improvements than ivacaftor alone, without further improvement in sweat chloride results.
To help understand why sweat chloride was unresponsive, the investigators will use a newly developed sweat secretion test that provides accurate, in vivo readout of CFTR (cystic fibrosis transmembrane conductance regulator) function in the sweat gland secretory coil.
The investigators devised a protocol to determine if short courses of ivacaftor (3.5 days) will produce significant increases in WT (Wild-Type, i.e. normal) CFTR open probability by measuring CFTR-dependent sweating (C-sweat) in subjects with WT CFTR.
|Condition or disease||Intervention/treatment||Phase|
|Cystic Fibrosis||Drug: Ivacaftor Drug: β-Adrenergic cocktail Drug: Pilocarpine Nitrate 5% Device: Macroduct sweat stimulator||Not Applicable|
Cystic fibrosis (CF) is a genetic disease caused by malfunctioning of a protein called CFTR.
CF affects various organs including the sweat glands and the lungs. An FDA approved drug called ivacaftor helps some people with CF, and laboratory tests show that it produces further improvement when combined with an investigational drug called lumacaftor. However, results from clinical tests of the two drugs used together gave mixed results: lung function improved but sweat gland function did not improve. This study will measure CFTR-dependent sweat rate to test the hypothesis that CFTR in the normal sweat glands might be functioning at peak efficiency, and so can't be improved further with ivacaftor, thus accounting for the apparent discrepancy between lung function and sweat gland results. CFTR-dependent sweat rate is important to understanding CF because it is a very accurate measure of CFTR function.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||(Study: Vertex IIS) A Study To Access the Effects of Ivacaftor on Wild Type CFTR-Open Probability (PO) In The Sweat Gland Secretory Coil|
|Actual Study Start Date :||July 31, 2015|
|Actual Primary Completion Date :||August 2, 2016|
|Actual Study Completion Date :||August 23, 2017|
Participants will receive ivacaftor orally for 3 days, followed by 35 days off drug. Participants will repeat this cycle then receive ivacaftor for 3 additional days. For sweat testing, participants will receive β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant will also receive pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing will be done on- and off-ivacaftor.
150mg administered orally twice daily.
Other Name: Kalydeco
Drug: β-Adrenergic cocktail
Administered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM).
Drug: Pilocarpine Nitrate 5%
Administered subcutaneously using Macroduct sweat stimulator device.
Device: Macroduct sweat stimulator
- Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate [ Time Frame: Up to 79 days ]CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data.
- Change Sweat Chloride Production [ Time Frame: Up to 79 days ]Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02310789
|United States, California|
|Stanford Hospital and Clinics|
|Stanford, California, United States, 94305|
|Principal Investigator:||Jeffrey Wine, PhD||Stanford University|